OPSINS, G PROTEIN PATHWAYS AND REGULATION IN RPE CELLS

RPE 细胞中的视蛋白、G 蛋白途径和调节

• 批准号: 2487834
• 负责人: HENRY K FONG
• 金额: $ 26.74万
• 依托单位: DOHENY EYE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2487834
• 关键词: G protein; circadian rhythms; gene expression; gene mutation; genetically modified animals; human tissue; immunocytochemistry; in situ hybridization; isomerase; laboratory mouse; laboratory rabbit; northern blottings; nucleic acid sequence; phospholipase C; protein binding; protein structure function; receptor coupling; retina disorder; retinal pigment epithelium; retinaldehyde; rhodopsin; tissue /cell culture; visual phototransduction; western blottings

DESCRIPTION (Adapted from applicant's abstract): Vertebrate RPE and Muller cells contain a cytoplasmic visual pigment homolog termed RGR (for RPE retinal G protein-coupled receptor) which binds retinoid and shares sequence similarity with retinochrome, a photoisomerase in squid photoreceptors. This application hypothesizes that RGR may function as a retinal isomerase in the vertebrate visual cycle, be involved in a primitive form of phototransduction, play a role in circadian rhythm, or act as a sensor of free retinaldehyde. To test these hypotheses, research will investigate RGR ligand- and protein-binding properties and analyze the phenotype resulting from mutation of the RGR gene in a RGR-less mouse model system. The endogenous chromophore of bovine RGR will be identified and photoisomerization of retinal bound to natural and recombinant RGR will be investigated. A splice variant of the human RGR gene termed RGR-d has been identified in which the predicted sixth transmembrane domain is deleted. To investigate the possibility that RGR-d is involved in diseases of the retina such as age-related macular degeneration (AMD), studies will characterize human RGR-d retinaldehyde-binding properties, subcellular localization and other possible altered properties.

描述（改编自申请人的摘要）：脊椎动物RPE和Muller 细胞包含称为RGR的细胞质视觉色素同源物（用于RPE 视网膜类似的视网膜G蛋白偶联受体）共享序列 与视网膜染色体（鱿鱼光感受器中的光异构酶）相似。 该应用程序假设RGR可以用作视网膜异构酶 在脊椎动物的视觉周期中，以原始形式参与 光转导，在昼夜节律中起作用或充当传感器 游离视网膜醛。 为了检验这些假设，研究将研究RGR 配体和蛋白质结合特性，并分析表型 从无RGR小鼠模型系统中的RGR基因的突变。 这 将确定牛RGR的内源性发色团，并 视网膜结合到天然和重组RGR的光异构化是 调查。 称为RGR-D的人RGR基因的剪接变体已是 鉴定在其中删除了预测的第六个跨膜结构域。 到 研究RGR-D参与视网膜疾病的可能性 例如与年龄相关的黄斑变性（AMD），研究将表征 人RGR-D视网膜结合特性，亚细胞定位和 其他可能改变的属性。